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Primary cilia

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https://www.readbyqxmd.com/read/29771182/ciliogenesis-is-reciprocally-regulated-by-ppara-and-nr1h4-fxr-through-controlling-autophagy-in-vitro-and-in-vivo
#1
Zhi-Qiang Liu, Joon No Lee, Myeongjoo Son, Jae-Young Lim, Raghbendra Kumar Dutta, Yunash Maharjan, SeongAe Kwak, Goo Taeg Oh, Kyunghee Byun, Seong-Kyu Choe, Raekil Park
The primary cilia are evolutionarily conserved microtubule-based cellular organelles that perceive metabolic status and thus link the sensory system to cellular signaling pathways. Therefore, ciliogenesis is thought to be tightly linked to autophagy, which is also regulated by nutrient-sensing transcription factors, such as PPARA (peroxisome proliferator activated receptor alpha) and NR1H4/FXR (nuclear receptor subfamily 1, group H, member 4). However, the relationship between these factors and ciliogenesis has not been clearly demonstrated...
May 17, 2018: Autophagy
https://www.readbyqxmd.com/read/29758252/depression-resistant-phenotype-in-mice-overexpressing-regulator-of-g-protein-signaling-8-rgs8
#2
Yuki Kobayashi, Risa Takemoto, Shogo Yamato, Tomoya Okada, Michihiko Iijima, Yoshikatsu Uematsu, Shigeyuki Chaki, Yumiko Saito
Regulator of G protein signaling (RGS) proteins are negative regulators of heterotrimeric G proteins that act by accelerating Gα-mediated GTPase activity to terminate G protein-coupled receptor-associated signaling. RGS8 is expressed in several brain regions involved with movement and mood. To investigate the role of RGS8 in vivo, we generated transgenic mice overexpressing brain RGS8 (RGS8tg). RGS8 gene and protein expressions were examined by real-time PCR and immunohistochemistry, respectively, and a significant increase in RGS8 protein was detected in the hippocampal CA1 region compared with wild-type mice (WT)...
May 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29752437/caspase-mediated-cleavage-of-the-centrosomal-proteins-during-apoptosis
#3
Mi Young Seo, Kunsoo Rhee
The centrosome is the major microtubule-organizing center and plays important roles in intracellular transport, cellular morphology, and motility. In mitotic cells, centrosomes function as spindle poles to pull a set of chromosomes into daughter cells. In quiescent cells, primary cilia are originated from the centrosomes. Given its involvement in various cellular processes, it is little surprising that the organelle would also participate in apoptotic events. However, it remains elusive how the centrosome changes in structure and organization during apoptosis...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29748385/activation-of-airway-epithelial-bitter-taste-receptors-by-pseudomonas-aeruginosa-quinolones-modulates-calcium-cyclic-amp-and-nitric-oxide-signaling
#4
Jenna R Freund, Corrine J Mansfield, Laurel J Doghramji, Nithin D Adappa, James N Palmer, David W Kennedy, Danielle R Reed, Peihua Jiang, Robert J Lee
Bitter taste receptors (T2Rs), discovered in many tissues outside the tongue, have recently become potential therapeutic targets. We showed previously that airway epithelial cells express several T2Rs that activate innate immune responses that may be important for treatment of airway diseases such as chronic rhinosinusitis. It is imperative to more clearly understand what compounds activate airway T2Rs as well as their full range of functions. T2R isoforms in airway motile cilia (T2Rs 4, 14, 16, and 38) produce bactericidal levels of nitric oxide (NO) that also increase ciliary beating, promoting clearance of mucus and trapped pathogens...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29745101/simulations-of-centriole-of-polarized-centrosome-as-a-monopole-antenna-in-immune-and-viral-synapses
#5
Josef Dvorak, Bohuslav Melichar, Alzbeta Filipova, Jana Grimova, Nela Grimova, Aneta Rozsypalova, David Buka, Rene Voboril, Radek Zapletal, Tomas Buchler, Igor Richter, David Buka
The immune synapse (IS) is a temporary interface between an antigen-presenting cell and an effector lymphocyte. Viral synapse is a molecularly organized cellular junction that is structurally similar to the IS. Primary cilium is considered as a functional homologue of the IS due to the morphological and functional similarities in architecture between both micotubule structures. It has been hypothesized that endogenous electromagnetic field in the cell is generated by a unique cooperating system between mitochondria and microtubules...
March 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29743590/loss-of-function-of-ift88-determines-metabolic-phenotypes-in-thyroid-cancer
#6
Junguee Lee, Shinae Yi, Minho Won, Young Shin Song, Hyon-Seung Yi, Young Joo Park, Ki Cheol Park, Jung Tae Kim, Joon Young Chang, Min Joung Lee, Hae Joung Sul, Ji Eun Choi, Koon Soon Kim, Jukka Kero, Joon Kim, Minho Shong
Primary cilia are microtubule-based, dynamic organelles characterized by continuous assembly and disassembly. The intraflagellar transport (IFT) machinery, including IFT88 in cilia, is involved in the maintenance of bidirectional motility along the axonemes, which is required for ciliogenesis and functional competence. Cancer cells are frequently associated with loss of primary cilia and IFT functions. However, there is little information on the role of IFT88 or primary cilia in the metabolic remodeling of cancer cells...
May 10, 2018: Oncogene
https://www.readbyqxmd.com/read/29742020/actin-dependent-regulation-of-cilia-length-by-the-inverted-formin-fhdc1
#7
Sarah J Copeland, Andrea McRae, Giulia Guarguaglini, Laura Trinkle-Mulcahy, John W Copeland
A primary cilium is found on most mammalian cells where it acts as a cellular antenna for the reception of both mechanical and chemical signals. A variety of diseases are associated with defective ciliogenesis reflecting the ubiquity of their function and the number of proteins required for cilia assembly. Proper cilia length is necessary for cilia signaling and is regulated through a poorly understood balance of assembly and disassembly rates. FHDC1 is a unique member of the formin family of cytoskeletal regulatory proteins...
May 9, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29742019/the-e3-ubiquitin-ligase-ubr5-regulates-centriolar-satellite-stability-and-primary-cilia
#8
Robert F Shearer, Kari-Anne Myrum Frikstad, Jessie McKenna, Rachael A McCloy, Niantao Deng, Andrew Burgess, Trond Stokke, Sebastian Patzke, Darren N Saunders
Primary cilia are crucial for signal transduction in a variety of pathways, including Hedgehog and Wnt. Disruption of primary cilia formation (ciliogenesis) is linked to numerous developmental disorders (known as ciliopathies) and diseases, including cancer. The Ubiquitin-Proteasome System (UPS) component UBR5 was previously identified as a putative positive regulator of ciliogenesis in a functional genomics screen. UBR5 is an E3 Ubiquitin ligase that is frequently deregulated in tumours, but its biological role in cancer is largely uncharacterised, partly due to a lack of understanding of interacting proteins and pathways...
May 9, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29734148/new-insights-into-cystic-kidney-diseases
#9
Toshio Mochizuki, Shiho Makabe, Yumi Aoyama, Hiroshi Kataoka, Kosaku Nitta
Hereditary cystic kidney diseases are considered as "ciliopathies" caused by abnormalities of the "primary cilia" situated on the tubules. As a result of dysplasia and dysfunction of cilia, formation of cysts occurs at various stages of life. Although occurring at a low incidence, hereditary cystic kidney diseases that develop from the fetal stage to childhood are diverse and are often associated with systemic disorders. The incidence of autosomal dominant polycystic kidney disease, which is the only adult-onset hereditary cystic kidney disease, is the highest among hereditary renal disorders...
2018: Contributions to Nephrology
https://www.readbyqxmd.com/read/29731308/nup98-sets-the-size-exclusion-diffusion-limit-through-the-ciliary-base
#10
S Joseph Endicott, Martina Brueckner
The primary cilium maintains a well-regulated complement of soluble and membrane proteins, allowing it to mediate a variety of signaling pathways that are essential for development and tissue homeostasis [1-3]. Entry into the cilium is regulated at the base, where a complex containing nucleoporins, referred to as the "ciliary pore complex" (CPC), has been proposed to set a size-exclusion limit for soluble molecule diffusion into the cilium [4-6]. Here, using a fluorescence-based diffusion trap system, we demonstrate that NUP98, a component of the phenylalanine-glycine (FG) hydrogel permeability barrier at the nuclear pore complex [7, 8], limits the diffusion of soluble molecules >70 kDa into the cilium in cultured mammalian cells...
April 26, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29729840/synergistic-mechano-chemical-sensing-by-vascular-cilia
#11
Gautier Follain, Jacky G Goetz
Endothelial cells can sense and respond to blood flow forces and signals, but the exact mechanisms employed remain poorly understood. A recent study describes how low-flow forces are sensed by primary cilia during development of the retinal vasculature, which sensitizes endothelial cells to BMP signaling.
May 2, 2018: Trends in Cell Biology
https://www.readbyqxmd.com/read/29727693/mutations-in-c11orf70-cause-primary-ciliary-dyskinesia-with-randomization-of-left-right-body-asymmetry-due-to-defects-of-outer-and-inner-dynein-arms
#12
Inga M Höben, Rim Hjeij, Heike Olbrich, Gerard W Dougherty, Tabea Nöthe-Menchen, Isabella Aprea, Diana Frank, Petra Pennekamp, Bernd Dworniczak, Julia Wallmeier, Johanna Raidt, Kim G Nielsen, Maria C Philipsen, Francesca Santamaria, Laura Venditto, Israel Amirav, Huda Mussaffi, Freerk Prenzel, Kaman Wu, Zeineb Bakey, Miriam Schmidts, Niki T Loges, Heymut Omran
Primary ciliary dyskinesia (PCD) is characterized by chronic airway disease, male infertility, and randomization of the left/right body axis as a result of defects of motile cilia and sperm flagella. We identified loss-of-function mutations in the open-reading frame C11orf70 in PCD individuals from five distinct families. Transmission electron microscopy analyses and high-resolution immunofluorescence microscopy demonstrate that loss-of-function mutations in C11orf70 cause immotility of respiratory cilia and sperm flagella, respectively, as a result of the loss of axonemal outer (ODAs) and inner dynein arms (IDAs), indicating that C11orf70 is involved in cytoplasmic assembly of dynein arms...
May 3, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29727692/c11orf70-mutations-disrupting-the-intraflagellar-transport-dependent-assembly-of-multiple-axonemal-dyneins-cause-primary-ciliary-dyskinesia
#13
Mahmoud R Fassad, Amelia Shoemark, Pierrick le Borgne, France Koll, Mitali Patel, Mellisa Dixon, Jane Hayward, Charlotte Richardson, Emily Frost, Lucy Jenkins, Thomas Cullup, Eddie M K Chung, Michel Lemullois, Anne Aubusson-Fleury, Claire Hogg, David R Mitchell, Anne-Marie Tassin, Hannah M Mitchison
Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disorder characterized by destructive respiratory disease and laterality abnormalities due to randomized left-right body asymmetry. PCD is mostly caused by mutations affecting the core axoneme structure of motile cilia that is essential for movement. Genes that cause PCD when mutated include a group that encode proteins essential for the assembly of the ciliary dynein motors and the active transport process that delivers them from their cytoplasmic assembly site into the axoneme...
May 3, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29727300/rab23-and-developmental-disorders
#14
Catherine H H Hor, Bor Luen Tang, Eyleen L K Goh
Rab23 is a conserved member of the Rab family of small GTPases that regulates membrane trafficking in eukaryotes. It is unique amongst the Rabs in terms of its implicated role in mammalian development, as originally illustrated by the embryonic lethality and open neural tube phenotype of a spontaneous mouse mutant that carries homozygous mutation of open brain, a gene encoding Rab23. Rab23 was initially identified to act as an antagonist of Sonic hedgehog (Shh) signaling, and has since been implicated in a number of physiological and pathological roles, including oncogenesis...
May 4, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29725084/loss-of-tctn3-causes-neuronal-apoptosis-and-neural-tube-defects-in-mice
#15
Bin Wang, Yingying Zhang, Hongli Dong, Siyi Gong, Bin Wei, Man Luo, Hongyan Wang, Xiaohui Wu, Wei Liu, Xingshun Xu, Yufang Zheng, Miao Sun
Tctn3 belongs to the Tectonic (Tctn) family and is a single-pass membrane protein localized at the transition zone of primary cilia as an important component of ciliopathy-related protein complexes. Previous studies showed that mutations in Tctn1 and Tctn2, two members of the tectonic family, have been reported to disrupt neural tube development in humans and mice, but the functions of Tctn3 in brain development remain elusive. In this study, Tctn3 knockout (KO) mice were generated by utilizing the piggyBac (PB) transposon system...
May 3, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29723155/a-pilot-study-exploring-the-impact-of-cardiac-medications-on-ciliary-beat-frequency-possible-implications-for-clinical-management
#16
Rohit S Loomba, Abhinav Bhushan, Adeleye J Afolayan
BACKGROUND: Cilia are involved in several physiologic processes, and at least a single primary cilium can be found on nearly every cell in the human body. Various factors, such as pH, temperature, exposure to medications and toxins can impact ciliary function as is manifested by changes in the ciliary beat frequency. Those with ciliary dyskinesia may also have congenital cardiac malformations and may require care in a cardiac intensive care unit. This study investigates the effect on the ciliary beat frequency of medications frequently used in a cardiac intensive care unit...
May 3, 2018: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29718757/arl2bp-a-protein-linked-to-retinitis-pigmentosa-is-needed-for-normal-photoreceptor-cilia-doublets-and-outer-segment-structure
#17
Abigail R Moye, Ratnesh Singh, Victoria A Kimler, Tanya L Dilan, Daniella Munezero, Thamaraiselvi Saravanan, Andrew F X Goldberg, Visvanathan Ramamurthy
The outer segment (OS) of photoreceptor cells is an elaboration of a primary cilium with organized stacks of membranous discs that contain the proteins needed for phototransduction and vision. Though cilia formation and function has been well characterized, little is known about the role of cilia in the development of photoreceptor OS. Nevertheless, progress has been made by studying mutations in ciliary proteins which often result in malformed outer segments and lead to blinding diseases. To investigate how ciliary proteins contribute to outer segment formation, we generated a knockout mouse model for ARL2BP, a ciliary protein linked to Retinitis Pigmentosa...
May 2, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29713460/sensing-the-cilium-digital-capture-of-ciliary-data-for-comparative-genomics-investigations
#18
Karen R Christie, Judith A Blake
Background: Cilia are specialized, hair-like structures that project from the cell bodies of eukaryotic cells. With increased understanding of the distribution and functions of various types of cilia, interest in these organelles is accelerating. To effectively use this great expansion in knowledge, this information must be made digitally accessible and available for large-scale analytical and computational investigation. Capture and integration of knowledge about cilia into existing knowledge bases, thus providing the ability to improve comparative genomic data analysis, is the objective of this work...
2018: Cilia
https://www.readbyqxmd.com/read/29712905/spatiotemporal-manipulation-of-ciliary-glutamylation-reveals-its-roles-in-intraciliary-trafficking-and-hedgehog-signaling
#19
Shi-Rong Hong, Cuei-Ling Wang, Yao-Shen Huang, Yu-Chen Chang, Ya-Chu Chang, Ganesh V Pusapati, Chun-Yu Lin, Ning Hsu, Hsiao-Chi Cheng, Yueh-Chen Chiang, Wei-En Huang, Nathan C Shaner, Rajat Rohatgi, Takanari Inoue, Yu-Chun Lin
Tubulin post-translational modifications (PTMs) occur spatiotemporally throughout cells and are suggested to be involved in a wide range of cellular activities. However, the complexity and dynamic distribution of tubulin PTMs within cells have hindered the understanding of their physiological roles in specific subcellular compartments. Here, we develop a method to rapidly deplete tubulin glutamylation inside the primary cilia, a microtubule-based sensory organelle protruding on the cell surface, by targeting an engineered deglutamylase to the cilia in minutes...
April 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29706353/patient-ipsc-derived-kidney-organoids-show-functional-validation-of-a-ciliopathic-renal-phenotype-and-reveal-underlying-pathogenetic-mechanisms
#20
Thomas A Forbes, Sara E Howden, Kynan Lawlor, Belinda Phipson, Jovana Maksimovic, Lorna Hale, Sean Wilson, Catherine Quinlan, Gladys Ho, Katherine Holman, Bruce Bennetts, Joanna Crawford, Peter Trnka, Alicia Oshlack, Chirag Patel, Andrew Mallett, Cas Simons, Melissa H Little
Despite the increasing diagnostic rate of genomic sequencing, the genetic basis of more than 50% of heritable kidney disease remains unresolved. Kidney organoids differentiated from induced pluripotent stem cells (iPSCs) of individuals affected by inherited renal disease represent a potential, but unvalidated, platform for the functional validation of novel gene variants and investigation of underlying pathogenetic mechanisms. In this study, trio whole-exome sequencing of a prospectively identified nephronophthisis (NPHP) proband and her parents identified compound-heterozygous variants in IFT140, a gene previously associated with NPHP-related ciliopathies...
April 21, 2018: American Journal of Human Genetics
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